Various implantable medical devices and minimally-invasive methods of transcatheter implantation of these devices have been developed to deliver medical devices within the lumen of a body vessel. These devices are advantageously inserted intravascularly, for example from an implantation catheter. Implantable medical devices can function as a stent to hold open an occluded or narrowed body vessel. Such devices can comprise an expandable frame configured for implantation in the lumen of a body vessel and a graft material attached to the frame. Various conditions, such as peripheral vascular disease and creation or reinforcement of hemodialysis fistulas, can be ameliorated by implantation of a medical device within a body vessel to provide a stenting function therein.
Peripheral vascular disease (PVD) is a condition with variable morbidity affecting mostly men and women older than 50 years. Peripheral vascular disease of the lower extremities may cause a variety of clinical indications from asymptomatic patients to patients with chronic critical limb ischemia (CLI) that might result in amputation and limb loss. Critical limb ischemia may impair the patient functional status and quality of life, and may be associated with an increased cardiovascular mortality and morbidity. Critical limb ischemia may be a chronic condition accompanied by acute conditions such as distal embolization, external compression, or acute thrombosis. Based on incidence rates extrapolated to today's increasingly aging population, PVD may affect as many as 10 million people in the United States (Becker G J, McClenny T E, Kovacs M E, et al., “The importance of increasing public and physician awareness of peripheral arterial disease,” J Vasc Interv Radiol., 13(1):7-11 (January 2002)). As the population ages, the family physician may be faced with increasing numbers of patients complaining of symptoms of lower extremity PVD. Nearly one in four of the approximately 60,000 people screened annually through Legs for Life, a nationwide screening program, are believed to be at moderate to high risk of lower extremity PVD and are referred to their primary care physicians for diagnosis (data collected by the Society of Cardiovascular and Interventional Radiology) (Becker G J, McClenny T E, Kovacs M E, et al., “The importance of increasing public and physician awareness of peripheral arterial disease,” J Vasc Interv Radiol., 13(1):7-11 (January 2002)).
Chronic critical limb ischemia may be defined not only by the clinical symptoms, but also by an objective measurement of impaired blood flow. Criteria for diagnosis include either one of the following: (1) more than two weeks of recurrent foot pain at rest that requires regular use of analgesics and is associated with an ankle systolic pressure of 50 mm Hg or less, or a toe systolic pressure of 30 mm Hg or less, or (2) a nonhealing wound or gangrene of the foot or toes, with similar hemodynamic measurements. The hemodynamic parameters may be less reliable in patients with diabetes because arterial wall calcification can impair compression by a blood pressure cuff and produce systolic pressure measurements that are greater than the actual levels. Ischemic rest pain is classically described as a burning pain in the ball of the foot and toes that is worse at night when the patient is in bed. The pain is exacerbated by the recumbent position because of the loss of gravity-assisted flow to the foot. Ischemic rest pain is located in the foot, where tissue is farthest from the heart and distal to the arterial occlusions. Patients with ischemic rest pain often need to dangle their legs over the side of the bed or sleep in a recliner to regain gravity-augmented blood flow and relieve the pain. Patients who keep their legs in a dependent position for comfort often present with considerable edema of the feet and ankles. Nonhealing wounds are usually found in areas of foot trauma caused by improperly fitting shoes or an injury. A wound is generally considered to be nonhealing if it fails to respond to a four- to 12-week trial of conservative therapy such as regular dressing changes, avoidance of trauma, treatment of infection and débridement of necrotic tissue. Gangrene may be found on the toes, occurring when the blood supply is so low that spontaneous necrosis occurs in the most poorly perfused tissues.
Treatment and prognosis of peripheral vascular disease can be influenced by lesion and patient characteristics, such as the site of the lesion, type of lesion (stenosis or occlusion, lesion length), arterial runoff, and clinical manifestation (Dormandy J A, Rutherford R B., “Management of peripheral arterial disease (PAD): TASC Working Group,” J Vasc Surg, 31(1 pt 2):S103-S106 (2000)). Estimates of the 5-year patency rate of balloon dilation for femoropopliteal arterial disease range from as low as 12% in patients with an occlusion and critical ischemia to 68% in patients with a stenosis and claudication (Hunink M G M, Wong J B, Donaldson M C, Meyerovitz M F, Harrington D P., “Patency results of percutaneous and surgical revascularization for femoropopliteal arterial disease,” Med Decis Making, 14:71-81 (1994)). Bypass surgery for femoropopliteal arterial disease has been associated not only with higher long-term patency rates but also with a higher procedural morbidity, mortality, and a longer hospital stay (Hunink M G M, Wong J B, Donaldson M C, Meyerovitz M F, de Vries J A, Harrington D P., “Revascularization for femoropopliteal disease, A decision and cost-effectiveness analysis,” Journal of the American Medical Assoc., 274:165-171 (1995)).
Implantable medical devices comprising an implantable frame and attached graft material may also be configured to provide for the creation or the repair of hemodialysis fistulas. Patients with chronic renal failure can require regular hemodialysis. These patients often have a vascular access graft surgically placed in the arm to provide a high flow site for dialysis. Over time, the accesses can narrow and block off (occlude) due to buildup of intimal hyperplasia (scar tissue). Failing or occluded dialysis access grafts can cause morbidity, discomfort, or inconvenience for dialysis patients due to the need for invasive procedures to reestablish access flow, or to graft abandonment and reoperation. When failure occurs, per National Kidney Foundation Guidelines, an interventional radiologist normally performs a balloon angioplasty to reopen the fistula and regain access for dialysis. Many patients who are not candidates for renal transplantation or those for whom a compatible donor cannot be secured may be dependent on hemodialysis for their lifetime. This situation may result in the long-term need for and use of the dialysis access. Preservation of patent well-functioning dialysis fistulas is a challenging clinical problem in the long-term treatment of patients undergoing dialysis. Hospital admissions in the dialysis population have been attributed to vascular access problems, including fistula malfunction and thrombosis.
Native fistula or graft malfunction and thrombosis can be treated by using surgical thrombectomy and revision, or percutaneous techniques such as balloon angioplasty (percutaneous transluminal angioplasty [PTA]), thrombolysis, and mechanical thrombectomy. Implantation of medical devices configured as implantable stent grafts can prolong the patency of the vascular access and decreasing the morbidity and mortality of patients with chronic renal failure.
Various implantable medical devices can be endovascularly inserted within various body vessels from an implantation catheter. Minimally invasive techniques and instruments for placement of intraluminal medical devices have been developed to treat and repair such undesirable conditions within body vessels. Intraluminal medical devices can be introduced to a point of treatment within a body vessel using a delivery catheter device passed through the blood vessels communicating between a remote introductory location and the implantation site, and released from the delivery catheter device at the point of treatment within the body vessel. Intraluminal medical devices can be deployed in a vessel at a point of treatment, the delivery device withdrawn from the vessel, and the medical device retained within the vessel to provide sustained improvement in vascular function or to increase vessel patency. However, the implantation of medical devices within blood vessels can be complicated by incidence of inflammation or thrombus formation in the blood vessel proximate the site of implantation. Heightened incidence of inflammatory response may accompany implantation of frames that remain within a body vessel, such as a metallic or biostable stent. Thrombus formation on the implanted medical device can result in compromised medical device function, or other medical complications.
The formation of blood clots, or thrombus, on the surface of an endovascular prosthesis can both degrade the intended performance of the prosthesis and even undesirably restrict or occlude desirable fluid flow within a body vessel. Inhibiting or preventing thrombosis and platelet deposition on an implantable device within the body is important in promoting continued function of the medical device within the body, particularly within blood vessels. Post-implantation thrombosis and platelet deposition on surfaces of implantable medical devices prosthesis may undesirably reduce the patency rate of many implantable medical devices. For example, thrombosis and platelet deposition within an endovascular stent graft may occlude the conduit defined by the endovascular prosthesis. Many factors may contribute to thrombosis and platelet deposition on the surfaces of implanted prosthesis. The properties of the material or materials forming the endovascular prosthesis are believed to be one important factor that can contribute to the likelihood of undesirable levels of post-implantation thrombus formation or platelet deposition on the implanted device.
Implantable medical, or portions thereof, can advantageously comprise a bioabsorbable material for some applications. When an implanted medical device is only medically required for a limited period of time, medical devices can be designed to dissipate within the body vessel after the desired time period, typically on the order of up to about three months. Including a bioabsorbable material in the can allow for the decomposition or absorption of all or part of the support frame during a period subsequent to implantation in a body vessel. A bioabsorbable support frame can be used, for example, to avoid future surgical extraction of an implant that serves a temporary function or to provide a medical device with post-implantation properties, such as frame stiffness, that change with time as portions of the frame are absorbed. Medical devices formed from biodegradable polymers, such as poly(lactic acid) and the like, have been implanted to provide implantable frames that dissipate within a blood vessel after two to three months. However, intravascular implantation biodegradable polymer frames has been linked to undesirably high incidence of thrombus formation (T. Susawa et al., “Biodegradable intracoronary stents in adult dogs,” J. Am. Coll. Cardiol., 21:483 A (1993) and what has been characterized as a “significant inflammatory response” (A. Colombo et al., “Biodegradable Stents, ‘Fulfilling the Mission and Stepping Away,’” Circulation 102:371-373 (2000)). Biodegradable polymeric stents may also have a resistance to radial compression that is greater than metallic stents, which may irritate body vessels that are prone to frequent collapse or dynamic movement. The peripheral blood vessels, such as the femoral, popliteal or illiac arteries, may be subject to dynamic movement during blood flow and body movement.
Recently, metal materials have been developed that are bioabsorbable while still providing some of the advantages of mechanical durability provided by metal support frames. For example, U.S. Pat. No. 6,287,332 (Bolz et al) and published U.S. Patent Application Nos. US 2005/0266041A1 (Gerold et. al.), US 2004/0098108 A1 (Harder et al.), US 2002/0004060 A1 (Heublein et al.), US 2005/0079088 A1 (Wirth et al.), US 2006/0064160 A1 (Gerold et al.) and US 2004/0098108A1 (Harder et al.) disclose medical devices formed from various metal materials that are absorbed upon implantation in a body vessel, particularly in coronary arteries. Many of these medical devices are bioabsorbable coronary stents comprising magnesium alloys.
The implantation of bioabsorbable magnesium alloy can provide a hypothrombogenic material with desired levels of radial flexibility. Stents in porcine coronary arteries have been reported by Waksman et al., “Safety and efficacy of bioabsorbable magnesium alloy stents in porcine coronary arteries,” Catheter Cardiovasc Interv. Sep. 12, 2006 [Epub ahead of print; PubMED PMID: 16969879]. Magnesium is believed to play a role in cellular events involved in inflammation and thrombosis. For example, Mazur et al. recently reported that increases in extracellular magnesium concentration have been linked to decreases in inflammatory response (Mazur et al., “Magnesium and the inflammatory response: Potential physiopathological implications,” Arch Biochem Biophys. Apr. 19, 2006; [Epub ahead of print; PubMED PMID: 16712775]), and “a direct role of low magnesium in promoting endothelial dysfunction by generating a pro-inflammatory, pro-thrombotic and pro-atherogenic environment . . . .” (Mazur, et al., “Low magnesium promotes endothelial cell dysfunction: implications for atherosclerosis, inflammation and thrombosis,” Biochem. Biophys. ACTA, 1689(1): 13-21, May 24, 2004). In addition, in another report, Toft et al. found that “[m]agnesium has been shown to reduce platelet aggregation both in vitro and ex vivo, and this antiplatelet effect may be advantageous in the prevention of arterial thrombosis” (G. Toft, et al., “Intravenously and topically applied magnesium in the prevention of arterial thrombosis,” Thromb Res. 99(1):61-9 (Jul. 1, 2000)).
For some medical applications, implantation of a stent graft may be advantageous. A stent graft typically includes a frame and a graft material attached to the frame. The frame may be sinusoidal hoop member attached to a tubular graft material. Typically, stent grafts are formed from metallic frame members comprising a plurality of struts and bends, attached to a tubular flexible material to define a tubular fluid conduit. For treatment of many conditions, it is desirable that graft material comprise remodelable material, permitting tissue ingrowth and absorption of the graft material within the body vessel over time. Implanted remodelable material provides a matrix or support for the growth of new tissue thereon, and remodelable material is resorbed into the body in which the device is implanted. Common events during this remodeling process include: widespread neovascularization, proliferation of granulation mesenchymal cells, biodegradation/resorption of implanted remodelable material, and absence of immune rejection. By this process, autologous cells from the body can replace the remodelable portions of the medical device. A variety of remodelable materials are available for use in implantable medical devices. Naturally derived or synthetic collagenous materials can be used to provide remodelable surfaces on implantable medical devices. Naturally derived or synthetic collagenous material, such as extracellular matrix material, are another category of remodelable materials that include, for instance, submucosa, renal capsule membrane, dura mater, pericardium, serosa, and peritoneum or basement membrane materials. One specific example of an extracellular matrix material is small intestine submucosa (SIS). When implanted, SIS can undergo remodeling and can induce the growth of endogenous tissues upon implantation into a host.
What are needed for some medical applications are medical devices having a support frame comprising a bioabsorbable material with thromboresistant properties and a remodelable graft material. Preferably, the medical device is configured as an implantable stent graft with a bioabsorbable metallic frame attached to an extracellular matrix material. In particular, endovascularly-implantable stent grafts that are completely bioabsorbable within the body vessel after a desired period of time, are particularly desirable for treatment of conditions such as PVD or CLI.